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<b>Abstract</b>— <p>Loss of macroautophagy and loss of proteostasis are hallmarks of aging. Lysosomal dysfunction is one of the reasons for the accumulation of non-degradable defective macromolecules, protein aggregates, and damaged organelles in the cells of organisms. The summary of experimental data obtained so far indicates an age-dependent weakening of lysosomal function. We hypothesize that lysosomes, as part of the autophagy and signaling network, are of great importance for longevity. In this review, we summarize information on the mechanisms of lysosomal influence on the lifespan and existing approaches to stimulate lysosomal function for longevity. We emphasize that factors such as intraluminal pH and interactions of lysosome-associated regulatory proteins (mTOR, AMPK, TFEB, and others) are related to aging. Stimulation of lysosomal function by dietary restriction, pharmacological or optogenetic approaches could be one of the promising interventions for anti-aging protection. In particular, a novel group of lysosomal optogenetic tools with high specificity of action could be a breakthrough in aging research.</p>

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Lysosome Functioning as a Process that Slows Down Aging

  • 期刊论文

  • 发表日期：

    2025年3月1日

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  • V. A. Alekhin,
  • S. F. Nazarova,
  • D. R. Gizatullina,
  • E. T. Lopatina,
  • M. P. Kirpichnikov,
  • M. A. Ostrovsky,
  • V. I. Gordeliy,
  • N. S. Ilyinsky

摘要

Abstract—

Loss of macroautophagy and loss of proteostasis are hallmarks of aging. Lysosomal dysfunction is one of the reasons for the accumulation of non-degradable defective macromolecules, protein aggregates, and damaged organelles in the cells of organisms. The summary of experimental data obtained so far indicates an age-dependent weakening of lysosomal function. We hypothesize that lysosomes, as part of the autophagy and signaling network, are of great importance for longevity. In this review, we summarize information on the mechanisms of lysosomal influence on the lifespan and existing approaches to stimulate lysosomal function for longevity. We emphasize that factors such as intraluminal pH and interactions of lysosome-associated regulatory proteins (mTOR, AMPK, TFEB, and others) are related to aging. Stimulation of lysosomal function by dietary restriction, pharmacological or optogenetic approaches could be one of the promising interventions for anti-aging protection. In particular, a novel group of lysosomal optogenetic tools with high specificity of action could be a breakthrough in aging research.